Dear MD Hoet,

Thank you very much for submitting your manuscript "The changing epidemiology of human monkeypox – a potential threat? A systematic review" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Gregory Gromowski

Associate Editor

PLOS Neglected Tropical Diseases

A. Desiree LaBeaud

Deputy Editor

PLOS Neglected Tropical Diseases

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Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: It was a well designed systematic review of the literature on monkeypox that was registered with PROSPERO

Reviewer #2: The manuscript presents a systematic review of monkeypox epidemiology with a focus on changes in the evolution since the first cases in the 1970s through the time of research. The review followed the PRISMA guideline and was prospectively registered with PROSTERO. The methods are well-explained. The study design, defined population (Africa and Ex-Africa) and analysis are appropriate for the study objective.

Competing interest by the funder and initiator of the study, Bavarian Nordic ( manufacturers of monkeypox vaccines) and the authors are declared.

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Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: The analysis was thorough, informative and well presented. The information presented is timely.

Reviewer #2: The analysis is descriptive and matches the analysis plan. However, there are some missing components that are critical.

Given the focus on describing the epidemiology of monkeypox, one gap was an absence of an analysis of genomics of the virus. An important recommendation for the authors to consider is an appraisal of the genetic evolution of the virus. Some studies to consider include: https://doi.org/10.1093/infdis/jiaa559 ; https://doi.org/10.3201/eid2002.130118, https://doi.org/10.1016/S1473-3099(18)30043-4

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Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: Conclusions were well supported by the results cited. Resurgence of monkeypox is an important public health issue.

Reviewer #2: The conclusion emphasised the available information and the need for improved surveillance to better understand the epidemiology of the disease

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Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: One minor issue concerns the authors statement on lines 483-484 that unvaccinated individuals accounted for approximately 80-96% of monkeypox cases. The authors should explain and document in more detail how this percentage range was determined.

Reviewer #2: Figure 2,3,4,5,6 would be better presented in a table for better readability

Line 318 - article should be articles

Line 419-421 - The statement " Conflicting findings of significance, however, were reported regarding direct exposure or touching the animal or having received a bite or scratch sufficient to break the skin" is not clear. Please, state the conflict being referred to. Though this is mentioned in the discussion, it needs to be stated in the results.

References 38 and 39 are same - please, edit.

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Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: This was a well-crafted, comprehensive review of the epidemiology of monkeypox which constitutes a valuable contribution to the field.

Reviewer #2: This is a relevant study which summarises available evidence of monkeypox epidemiology at a time of increasing awareness of ongoing transmission in Africa and exportation of cases with need for development of control strategies. Though a similar review was published in 2018 (cited), this study marginally more informational by including newly published works. Studies with phylogenetic analysis are excluded. Phylogenetic analysis is important to describe the evolution of monkeypox in the past 4-5 decades.

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Reviewer #1: No

Reviewer #2: No

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

Data Requirements:

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References

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article's retracted status in the References list and also include a citation and full reference for the retraction notice.

Dear MD Hoet,

We are pleased to inform you that your manuscript 'The changing epidemiology of human monkeypox – a potential threat? A systematic review' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Gregory Gromowski

Associate Editor

PLOS Neglected Tropical Diseases

A. Desiree LaBeaud

Deputy Editor

PLOS Neglected Tropical Diseases

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